AB0608 CIRCULATING LEVELS OF TNF/TNFR SUPERFAMILY FACTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ANTIPHOSPHOLIPID RELATED SYNDROMES
Authors: S. Bertocchi, E. Pedretti, T. Lowin, A. Caproli, S. Tamanini, F. Regola, A. Tincani, F. Franceschini, S. Piantoni, L. Andreoli, G. Pongratz
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> B-cell tolerance checkpoint defects are part of the pathomechanism in humoral autoimmune disorders, such as Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) [1]. In APS, despite the strong evidence of antibody mediated pathogenesis (aPL), specific B cell phenotype abnormalities, and the development of the disease in patients with inborn errors of immunity involving B cell ontogeny, data on the use of therapies directed toward B cells are still lacking and anticoagulation remains the corner stone of management [2]. <h3>Objectives</h3> The aim of this study was to measure serum levels of TNF/TNFR superfamily factors which are involved in B-cell homeostasis, looking for differences among diseases. <h3>Methods</h3> Two hundred and twenty-seven patients [75 SLE, 62 SLE+aPL, 36 SLE+APS and 54 primary APS (PAPS)] were enrolled. The dosage was performed by high-sensitivity ELISA. Data are expressed in median (pg/ml or ng/ml for sBCMA) (1<sup>st</sup>-3<sup>rd</sup> quartile). P values≤0.05 were considered statistically significant (*). <h3>Results</h3> SLE patients had BAFF serum levels=316.61 (200.96-579.87) vs 359.26 (SLE+aPL), 615.87* (351.22-893) (SLE+APS), 483.31* (328.02-745.5) (PAPS); APRIL=4563.53 (3028.04-6236.94) vs 5080.33, 3142.60, 3424.06* (1278.25-5800.38); sBCMA=11891.15 (8859.21-15630.50) vs 14991.55, 10372.41, 14632.88; sTACI=357.37 (255.05-905.78) vs 450.51, 424.00, 486.43; sCD40L=1355.97 (651.77-2673.81) vs 985.42* (498.92-1746.94), 1023.00, 691.96* (258.19-1329.79); TWEAK=2477.49 (1772.76-3069.27) vs 2454.60, 1683.09* (583-2814.55), 2171.18. In a linear regression model including sBCMA, sTACI, BAFF, sCD40L and TWEAK as predictors, only sBCMA was associated positively with IgG anticardiolipin (p=0.003) and IgG antibeta2-glycoprotein I (p&lt;0.001). In second approach a linear regression model was built, including diagnoses as predictor for respective TNFF member and potential cofounders BMI, gender, CRP, leukocyte levels, hormonal status and prednisone (mg/week). Levels of BAFF, sBCMA and sCD40L were clearly associated with the underlying diagnosis [predicted values for BAFF in SLE, SLE+aPL, SLE+APS, PAPS: 778.18 (p=0.007), 637.40 (p=0.035), 946.16 (p=0.002), 919.63 (p=0.005); for sBCMA: 9068.08 (p=0.004), 10655.50 (p=0.001), 8806.06 (p=0.009), 12131.52 (p=0.001); for sCD40L: 2464.84 (p&lt;0.001), 2025.37 (p=0.001), 2018.68 (p=0.001), 1943.45 (p=0.002)]. TWEAK was not associated with diagnosis or any of the other variables included in this model. APRIL was only associated with the diagnosis of SLE [3017.76 (p=0.016)] and SLE+APL [3531.74 (p=0.007)]. <h3>Conclusion</h3> Our study shows an association of TNF-family members with underlying diagnosis, which underscores the contribution of TNF-family members to pathogenesis. On the other hand, TNF-family members are also directly associated to certain anti-phospholipid antibodies with a significant positive association of the plasma cell activation marker sBCMA with IgG anticardiolipin and IgG antibeta2-glycoprotein I antibodies. Taken together, our results reinforcing the possible use of anti-B cell therapies in antiphospholipid related syndromes. <h3>Reference</h3> [1]Yanaba K, et al. Immunol Rev. 2008; 2. Dieudonné Y, et al. Autoimmun Rev. 2021 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.